Oral administration of drugs and vaccines offers several advantages. Dosages could be administered to a large number of animals via the food or water with minimal restraint and labor. Restraint also stresses animals rendering the drug or vaccination less effective and increasing the risk of infectious disease. For meat-producing animals, oral administration has another advantage in that it avoids injection site reactions. Broken needles, contamination of the injection site, or the use of highly reactive adjuvants can induce abscesses that damage the carcass and the skins. These reactions decrease the value of the animal at slaughter. This is also an issue in fish vaccination programs where fish need to be harvested from their tanks or open sea cages and injected individually. Oral inoculation is quick and efficient and eliminates the need for multiple handling of animals to administer subsequent booster inoculations. Adverse immune reactions following oral administration are also much less likely to occur and are therefore safer.
Oral vaccination is a particularly cost effective way to vaccinate or treat a large number of fish at one time in fish aquaculture systems, with minimal stress or labor. This is especially true when oral administration of the vaccine can be effected through ingestion during the course of feeding/drinking. Further, oral vaccines can be manufactured more cost effectively than injectable vaccine formulations because of the fewer purification steps needed to generate an oral vaccine. Oral vaccination also offers the advantage of fewer side effects such as stress or other reactions to the injection.
Despite the advantages of oral administration of drugs and particularly vaccines, the development of the technology has been delayed by the lack of adequate vaccine delivery systems. In the absence of suitable delivery systems, most oral vaccines undergo degradation in the gastrointestinal (GI) tract, especially under low-pH stomach conditions, resulting in limited absorption, which in turn results in insufficient immune responses.
Historically, immunization has relied on the induction of humoral immunity by parenteral administration of vaccines. Antibodies induced by parenteral administrations do not, however, necessarily reach mucosal surfaces, the sites of entry of most infectious agents. Mucosal immunity, which develops at mucosal surfaces including the intestine, lung, mouth, eye, mammary gland, and the genitourinary tract, and also skin and gill in fish, as a result of contact of antigen with mucosal tissues, is an important first line of defense against infectious agents.
Various vehicles have been developed to deliver drugs or vaccines to the gut-mucosal tissues. Biodegradable polymers, such as poly-(DL-lactide) and poly-(DL-lactide-co-glycolide), have been used to produce compositions for oral administration of antigens. However, production of these polymer particles requires the use of solvents that can harm fragile antigens. Furthermore, the use of solvents prevents the incorporation of attenuated live organisms, such as viruses or bacteria, within those compositions.
Other challenges of developing adequate oral delivery systems include the need to select only food or feed grade and biodegradable compounds and adjuvants, and the need for a long-lasting and robust immune response.